Exploratory studies of ab initio protein structure prediction: Multiple copy simulated annealing, AMBER energy functions, and a generalized born/solvent accessibility solvation model

Abstract Background Accurate prediction of protein tertiary structures is highly desired as the knowledge of protein structures provides invaluable insights into protein functions. We have designed two approaches to protein structure prediction, including a template-based modeling approach (called ProALIGN) and an ab initio prediction approach (called ProFOLD). Briefly speaking, ProALIGN aligns a target protein with templates through exploiting the patterns of context-specific alignment motifs and then builds the final structure with reference to the homologous templates. In contrast, ProFOLD uses an end-to-end neural network to estimate inter-residue distances of target proteins and builds structures that satisfy these distance constraints. These two approaches emphasize different characteristics of target proteins: ProALIGN exploits structure information of homologous templates of target proteins while ProFOLD exploits the co-evolutionary information carried by homologous protein sequences. Recent progress has shown that the combination of template-based modeling and ab initio approaches is promising. Results In the study, we present FALCON2, a web server that integrates ProALIGN and ProFOLD to provide high-quality protein structure prediction service. For a target protein, FALCON2 executes ProALIGN and ProFOLD simultaneously to predict possible structures and selects the most likely one as the final prediction result. We evaluated FALCON2 on widely-used benchmarks, including 104 CASP13 (the 13th Critical Assessment of protein Structure Prediction) targets and 91 CASP14 targets. In-depth examination suggests that when high-quality templates are available, ProALIGN is superior to ProFOLD and in other cases, ProFOLD shows better performance. By integrating these two approaches with different emphasis, FALCON2 server outperforms the two individual approaches and also achieves state-of-the-art performance compared with existing approaches. Conclusions By integrating template-based modeling and ab initio approaches, FALCON2 provides an easy-to-use and high-quality protein structure prediction service for the community and we expect it to enable insights into a deep understanding of protein functions.

Download Full-text

AIMOES: Archive information assisted multi-objective evolutionary strategy for ab initio protein structure prediction

Knowledge-Based Systems ◽

10.1016/j.knosys.2018.01.028 ◽

2018 ◽

Vol 146 ◽

pp. 58-72 ◽

Cited By ~ 17

Author(s):

Shuangbao Song ◽

Shangce Gao ◽

Xingqian Chen ◽

Dongbao Jia ◽

Xiaoxiao Qian ◽

...

Keyword(s):

Protein Structure ◽

Ab Initio ◽

Protein Structure Prediction ◽

Structure Prediction ◽

Evolutionary Strategy ◽

Multi Objective

Download Full-text

Protein Structure Prediction

Biotechnology ◽

10.4018/978-1-5225-8903-7.ch007 ◽

2019 ◽

pp. 156-184

Author(s):

Hirak Jyoti Chakraborty ◽

Aditi Gangopadhyay ◽

Sayak Ganguli ◽

Abhijit Datta

Keyword(s):

Protein Structure ◽

Ab Initio ◽

Protein Structure Prediction ◽

Structure Prediction ◽

Future Research ◽

Computational Techniques ◽

Target Sequence ◽

Knowledge Based ◽

Research Areas ◽

Three Phases

The great disagreement between the number of known protein sequences and the number of experimentally determined protein structures indicate an enormous necessity of rapid and accurate protein structure prediction methods. Computational techniques such as comparative modeling, threading and ab initio modelling allow swift protein structure prediction with sufficient accuracy. The three phases of computational protein structure prediction comprise: the pre-modelling analysis phase, model construction and post-modelling refinement. Protein modelling is primarily comparative or ab initio. Comparative or template-based methods such as homology and threading-based modelling require structural templates for constructing the structure of a target sequence. The ab initio is a template-free modelling approach which proceeds by satisfying various physics-based and knowledge-based parameters. The chapter will elaborate on the three phases of modelling, the programs available for performing each, issues, possible solutions and future research areas.

Download Full-text

Protein Structure Prediction

Advances in Bioinformatics and Biomedical Engineering - Applying Big Data Analytics in Bioinformatics and Medicine ◽

10.4018/978-1-5225-2607-0.ch003 ◽

2018 ◽

pp. 48-79 ◽

Cited By ~ 1

Author(s):

Hirak Jyoti Chakraborty ◽

Aditi Gangopadhyay ◽

Sayak Ganguli ◽

Abhijit Datta

Keyword(s):

Protein Structure ◽

Ab Initio ◽

Protein Structure Prediction ◽

Structure Prediction ◽

Future Research ◽

Computational Techniques ◽

Target Sequence ◽

Knowledge Based ◽

Research Areas ◽

Three Phases

The great disagreement between the number of known protein sequences and the number of experimentally determined protein structures indicate an enormous necessity of rapid and accurate protein structure prediction methods. Computational techniques such as comparative modeling, threading and ab initio modelling allow swift protein structure prediction with sufficient accuracy. The three phases of computational protein structure prediction comprise: the pre-modelling analysis phase, model construction and post-modelling refinement. Protein modelling is primarily comparative or ab initio. Comparative or template-based methods such as homology and threading-based modelling require structural templates for constructing the structure of a target sequence. The ab initio is a template-free modelling approach which proceeds by satisfying various physics-based and knowledge-based parameters. The chapter will elaborate on the three phases of modelling, the programs available for performing each, issues, possible solutions and future research areas.

Download Full-text

AIDA: ab initio domain assembly for automated multi-domain protein structure prediction and domain–domain interaction prediction

Bioinformatics ◽

10.1093/bioinformatics/btv092 ◽

2015 ◽

Vol 31 (13) ◽

pp. 2098-2105 ◽

Cited By ~ 29

Author(s):

Dong Xu ◽

Lukasz Jaroszewski ◽

Zhanwen Li ◽

Adam Godzik

Keyword(s):

Protein Structure ◽

Ab Initio ◽

Protein Structure Prediction ◽

Structure Prediction ◽

Domain Interaction ◽

Interaction Prediction ◽

Domain Protein

Download Full-text